Researchers Uncover Molecular Mechanism Behind Highly Efficient Hydrogen-Producing Enzymes

Researchers from the Photobiotechnology group at Ruhr University Bochum in Germany have discovered how certain hydrogen-producing enzymes rapidly capture protons to facilitate chemical reactions. The study, led by Dr. Jifu Duan and Professor Thomas Happe, was reported in the Journal of the American Chemical Society on October 27, 2026.

Microbial enzymes known as hydrogenases generate hydrogen (H2) by combining protons and electrons. Some of these biocatalysts are capable of capturing nearly 10,000 protons per second. To understand this rapid intake, the research team examined how [FeFe]-hydrogenases interact with zinc, a metal ion known to bind to amino acid sites and potentially inhibit catalytic activity.

Using protein crystallography, molecular simulations, electrochemistry, and hydrogen production testing, the researchers found that zinc selectively inhibits the enzyme by binding at a specific location near the known proton transport pathway. This interaction blocked two specific histidine amino acids on the surface of the enzyme.

The researchers demonstrated that one of these histidines acts as a "molecular pendulum." Supported by another amino acid serving as a fixed fulcrum, this histidine swings toward the enzyme's surface to receive a proton from the second histidine, then swings inward to transfer the proton to the internal transport pathway. Modifying one of these histidines made the enzyme resistant to zinc inhibition, while modifying the other significantly slowed its ability to produce hydrogen.

According to the researchers, this pendulum mechanism appears to be exclusive to Group A [FeFe]-hydrogenases, which are known for exceptionally high production rates compared to other groups. The team noted that understanding this evolutionary adaptation could assist in the development of tailored biocatalysts for industrial bio-based processes and provide deeper insight into hydrogen metabolism within ecosystems.

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